The goal of this project is to use rodent models to elucidate the mechanisms underlying the behavioral effects of hallucinogenic drugs of abuse, including LSD and DOI,as well as natural products used in recreational, ritual, or religious contexts, including SMeODMT and Ayahuasca tea. Based on the profound effects of hallucinogens on responses to sensory and emotional stimuli, behavioral effects will be measured using a multivariate profile of exploratory and investigatory behavior provided by rat and mouse Behavioral Pattern Monitor systems. These computerized systems assess activity, exploration, and behavioral organization - three major aspects of rodent behavior in an open field. The project has two specific aims. The first aim is to characterize and identify the specific mechanisms by which LSD and synthetic equivalents of Ayahuasca ("Pharmahuasca") alter exploratory behavior in rats. These studies will extend initial investigations into the nature of the biphasic, LSD-like profile of Pharmahuasca, in which exploratory behavior is initially suppressed and then increases as time progresses. We will test whether metabolic interactions between Pharmahuasca components contribute to the LSD-like behavioral profile, or whether specific neurochemical or receptor interactions are involved. The second aim is to assess the respective contributions of 5HT1A and 5HT2A serotonin receptors to the effects of hallucinogens on exploratory and investigatory behavior in mice. Both selective antagonists and knockouts of 5HTIA and 5HT2A receptors will be studied in order to develop converging evidence to test the hypothesis that both receptors contribute to the behavioral effects. This research is designed to elucidate the neurobiological mechanisms responsible for the acute effects of hallucinogens, which are presumably responsible for the recreational use of these drugs of abuse. These studies should also further our basic understanding of the behavioral functions of serotonergic systems. Collectively, this work is consistent with the stated mission of NIDA to bring "thepower of science to bear on drug abuse and addiction." Additionally, the study of psychoactive properties of natural products has been identified by NIDA as a priority area for research. Relevance: The recreational use of hallucinogens is a concern from a public health standpoint. This work will further our understanding of the basic neural mechanisms mediating the behavioral effects of these drugs of abuse.